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Mendelian randomisation implicates hyperlipidaemia as a risk factor for colorectal cancer
Author(s) -
RodriguezBroadbent Henry,
Law Philip J.,
Sud Amit,
Palin Kimmo,
Tuupanen Sari,
Gylfe Alexandra,
Hänninen Ulrika A.,
Cajuso Tatiana,
Tanskanen Tomas,
Kondelin Johanna,
Kaasinen Eevi,
Sarin AnttiPekka,
Ripatti Samuli,
Eriksson Johan G.,
Rissanen Harri,
Knekt Paul,
Pukkala Eero,
Jousilahti Pekka,
Salomaa Veikko,
Palotie Aarno,
RenkonenSinisalo Laura,
Lepistö Anna,
Böhm Jan,
Mecklin JukkaPekka,
AlTassan Nada A.,
Palles Claire,
Martin Lynn,
Barclay Ella,
Farrington Susan M.,
Timofeeva Maria N.,
Meyer Brian F.,
Wakil Salma M.,
Campbell Harry,
Smith Christopher G.,
Idziaszczyk Shelley,
Maughan Timothy S.,
Kaplan Richard,
Kerr Rachel,
Kerr David,
Passarelli Michael N.,
Figueiredo Jane C.,
Buchanan Daniel D.,
Win Aung K.,
Hopper John L.,
Jenkins Mark A.,
Lindor Noralane M.,
Newcomb Polly A.,
Gallinger Steven,
Conti David,
Schumacher Fred,
Casey Graham,
Aaltonen Lauri A.,
Cheadle Jeremy P.,
Tomlinson Ian P.,
Dunlop Malcolm G.,
Houlston Richard S.
Publication year - 2017
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.30709
Subject(s) - medicine , odds ratio , colorectal cancer , single nucleotide polymorphism , confidence interval , risk factor , mendelian randomization , oncology , gastroenterology , endocrinology , cancer , genetics , biology , genotype , genetic variants , gene
While elevated blood cholesterol has been associated with an increased risk of colorectal cancer (CRC) in observational studies, causality is uncertain. Here we apply a Mendelian randomisation (MR) analysis to examine the potential causal relationship between lipid traits and CRC risk. We used single nucleotide polymorphisms (SNPs) associated with blood levels of total cholesterol (TC), triglyceride (TG), low‐density lipoprotein (LDL), and high‐density lipoprotein (HDL) as instrumental variables (IV). We calculated MR estimates for each risk factor with CRC using SNP‐CRC associations from 9,254 cases and 18,386 controls. Genetically predicted higher TC was associated with an elevated risk of CRC (odds ratios (OR) per unit SD increase = 1.46, 95% confidence interval [CI]: 1.20–1.79, p = 1.68 × 10 −4 ). The pooled ORs for LDL, HDL, and TG were 1.05 (95% CI: 0.92–1.18, p = 0.49), 0.94 (95% CI: 0.84–1.05, p = 0.27), and 0.98 (95% CI: 0.85–1.12, p = 0.75) respectively. A genetic risk score for 3‐hydoxy‐3‐methylglutaryl‐coenzyme A reductase ( HMGCR ) to mimic the effects of statin therapy was associated with a reduced CRC risk (OR = 0.69, 95% CI: 0.49–0.99, p = 0.046). This study supports a causal relationship between higher levels of TC with CRC risk, and a further rationale for implementing public health strategies to reduce the prevalence of hyperlipidaemia.